1. Field of the Invention
The present invention relates to methods for diagnosing and treating Helicobacter pylori infection, particularly relates to methods for detecting Helicobacter pylori neutrophil-activating protein (HP-NAP) and inhibiting the activity of HP-NAP by using an antibody.
2. The Prior Art
Helicobacter pylori (H. pylori) is a gram-negative, microaerophilic bacterium that may infect around one-third of the people in the world. According to epidemiology reports, more than ten million people are infected with H. pylori among healthy population in Taiwan. In a host, H. pylori colonizes the gastric mucosa of stomach and triggers inflammation. It is highly associated with the pathogenesis of acute and chronic gastritis, peptic ulcer, duodenitis, lymphoma, gastric adenocarcinoma and other gastric cancers. In 1994, World Health Organization (WHO) declared H. pylori as a Class I carcinogen. Thus, infection by H. pylori has become an essential public health issue.
The commonly used clinical tests for H. pylori infection include biopsy, gastroscopy, and urea breath test (UBT) with the use of carbon isotopes. Laboratory tests also include the gastric tissue culture and serological test. However, the gastric tissue culture may easily yield false positive or false negative results due to the operation process; the urea breath test is too expensive for developing countries. Although diagnosis by polymerase chain reaction (PCR) has been developed, this method is costly, time-consuming and not clinically applicable.
HP-NAP is a virulence factor produced by H. pylori strains. It is a dodecameric protein consisting of twelve identical subunits, each of which is a four-helix bundle with a molecular weight of 17 kDa. HP-NAP induces production of reactive oxygen species (ROS) by neutrophils through the activation of a pertussis toxin (PTX)-sensitive G protein-coupled receptor (GPCR). It is also a ligand of Toll-like receptor 2 (TLR2), which is involved in HP-NAP-induced release of interleukin-6 (IL-6) in splenocytes. HP-NAP also stimulates neutrophils to produce myeloperoxidase, chemokines and pro-inflammatory cytokines and induces neutrophil chemotaxis and neutrophil-endothelial adhesion. In addition, HP-NAP is able to activate monocytes and mast cells. The inflammatory mediators produced by these innate immune cells upon H. pylori infection can lead to gastric mucosal damage.
As a result, HP-NAP may be a potential target for diagnosis and treatment of H. pylori infection because of its important role in the pathogenesis of diseases initiated by H. pylori infection. Since there is an urgent need for fast and accurate diagnosis of H. pylori infection, development of new detection methods based on detecting HP-NAP may be the solution.